SteroTherapeutics Receives FDA Orphan-Drug Designation

Posted on April 4, 2018 by MaryO

PHILADELPHIA, April 04, 2018 — SteroTherapeutics, a privately held biopharmaceutical company developing therapies focused on metabolic diseases including non-alcoholic steatohepatitis (NASH), announced today that the U.S. Food and Drug Administration has granted orphan drug designation for ST-002 in the treatment of nonalcoholic fatty liver disease, nonalcoholic steatosis and hyperglycemia in patients with Cushing’s syndrome.

“We are pursuing a drug that has a very real potential to become the optimal agent of choice and a standard of care for these Cushing’s patients,” said Manohar Katakam Ph. D., CEO of SteroTherapeutics. “Our clinical trial will target multiple critical metabolic-related outcomes including the reduction of triglycerides, insulin resistance, weight loss, and the prevention and/or abrogation of hepatic steatosis and fibrosis.”

“The FDA’s orphan-drug designation for Fluasterone highlights the significant unmet and underserved needs for treatment in these individuals,” added Dr. Katakam. “We look forward to realizing the benefits and promise of this potential for Fluasterone in Cushing’s syndrome patients.”

The Orphan Drug Act became law in 1983. Fewer than 5,000 applicants have received this designation, according to the FDA website. Rare conditions are often described as orphan diseases or disorders when there are few or no treatment options. There are approximately 7,000 known orphan diseases.

The FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States.

The designation allows the sponsor of the drug to be eligible for various incentives, including a seven-year period of U.S. marketing exclusivity upon regulatory approval of the drug, as well as tax credits for clinical research costs, annual grant funding, clinical trial design assistance, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees.

Cushing syndrome occurs when a patient’s body is exposed to high levels of the hormone cortisol over a long period of time (chronic hypercortisolemia) . Cushing syndrome, sometimes called hypercortisolism, affects 15,000 to 20,000 patients in the United States.

Too much cortisol can produce some of the hallmark signs of Cushing syndrome — a fatty hump between a patient’s shoulders, a rounded face, and pink or purple stretch marks on the skin. Cushing syndrome can also result in high blood pressure, bone loss and upper body obesity, increased fat around the neck, and relatively slender arms and legs. Diabetes is frequently a complication found in Cushing’s syndrome patients. These patients also develop nonalcoholic fatty disease and steatosis as a result of the chronic hypercortisolism.

About SteroTherapeutics

SteroTherapeutics, a Philadelphia, PA area based company, is focused on developing novel therapies for significant unmet needs in metabolic disease including liver diseases.

SteroTherapeutics lead products have been proven in previous human studies to possess a strong safety profile and established mechanisms of action. The company’s strategic intent is to focus on understanding disease pathways and how to safely treat and restore an optimal quality of life.  SteroTherapeutics is managed by a veteran team that has significant experience in the pharmaceutical and biotechnology industry. The team has specific experiences in the development, manufacturing and commercialization of small molecule and biologics based products.

INVESTOR RELATIONS CONTACT:
Tony Schor, Investor Awareness, Inc. on behalf of
SteroTherapeutics, LLC
tschor@sterotx.com/ (847) 945-2222 ext. 221

From https://www.econotimes.com/SteroTherapeutics-Receives-FDA-Orphan-Drug-Designation-1236099

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Primary Adrenal Insufficiency (PAI)

Posted on May 6, 2017 by MaryO
05.05.2017, 05:18 by SciDoc Publishers International Journal of Clinical Therapeutics and Diagnosis (IJCTD)
 Al-Jurayyan NA
Background: Primary adrenal insufficiency (PAI) in children is an uncommon, but potentially fatal. The current symptoms include weakness, fatigue, anorexia, abdominal pain, weight loss, orthostatic hypotension, salt craving and characterized by hyperpigmentation.
Material and Methods: This is a retrospective, hospital based-study, conducted at King Khalid University Hospital (KKUH), during the period January 1989 and December 2014. Review of medical record of patient diagnosed with primary adrenal insufficiency. The diagnosis was based on medical history, physical examination and low levels of glucocorticoids and raised adrenocorticotropic hormone (ACTH). Appropriate laboratory and radiological investigations were also reviewed.
Results: During the period under review, January 1989 and December 2014, a total of 125 patients with the diagnosis of primary adrenal insufficiency were seen. Inherited disorders like congenital adrenal hyperplasia and hypoplasia were common, 85.5%. However, variable autoimmune mediated etiologic diagnosis accounted for, 13%, were also seen. The appropriate various laboratory and radiological investigations should be planned.
Conclusion: Although, congenital adrenal hyperplasia was the commonest etiology, however, congenital adrenal hypoplasia should not be over looked. The diagnosis of PAI can be challenging in some patients, and therefore appropriate serological and radiological investigations should be done.

REFERENCES

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Addison’s disease: Primary adrenal insufficiency

Posted on May 2, 2016 by MaryO

Abstract

Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease.

Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH.

Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises.

Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

From http://www.ncbi.nlm.nih.gov/pubmed/27129928

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Roundup may cause potentially fatal ‘adrenal insufficiency’

Posted on August 22, 2015 by MaryO

IMPORTANT!  A new study finds that the Roundup herbicide disrupts the hormonal system of rats at low levels at which it’s meant to produce no adverse effects. By the same mechanism It may be causing the potentially fatal condition of ‘adrenal insufficiency’ in humans.

Monsanto’s glyphosate-based herbicide Roundup is an endocrine (hormone) disruptor in adult male rats, a new study shows.

The lowest dose tested of 10 mg/kg bw/d (bodyweight per day) was found to reduce levels of corticosterone, a steroid hormone produced in the adrenal glands. This was only one manifestation of a widespread disruption of adrenal function.

No other toxic effects were seen at that dose, so if endocrine disruption were not being specifically looked for, there would be no other signs that the dose was toxic. However a 2012 study detected a 35% testosterone down-regulation in rats at a concentration of 1 part per million.

In both studies endocrine disruption was detected at the lowest level tested for, so we don’t know if, when it comes to endocrine disruption, there are ‘safe’ lower doses of Roundup. In technical parlance, this means that no NOAEL (no observed adverse effect level), was found.

Significantly, the authors believe that the hormonal disruption could lead to the potentially fatal condition know as ‘adrenal insufficiency’ in humans, which causes fatigue, anorexia, sweating, anxiety, shaking, nausea, heart palpitations and weight loss.

“A progressive increase in its prevalence has been observed in humans, while a very few studies relating to xenobiotic exposure and adrenal insufficiency development have been reported”, they write. The increasing levels of Roundup in the environment and food could be “one of the possible mechanisms of adrenal insufficiency.”

How does this level relate to safety limits set by regulators?

One problem with trying to work out how the endocrine disruptive level of 10 mg/kg bw/d relates to how ‘safe’ levels are set by regulators.

The experiment looked at Roundup, the complete herbicide formulation as sold and used, but regulators only look at the long-term safety of glyphosate alone, the supposed active ingredient of Roundup.

Safe levels for chronic exposure to the Roundup herbicide product have never been tested or assessed for regulatory processes. This is a serious omission because Roundup has been shown in many tests to be more disruptive to hormones than glyphosate alone, thanks to the numerous other ingredients it contains to enhance its weed-killing properties.

Given this yawning data gap, let’s for a moment assume that the regulatory limits set for glyphosate alone can be used as a guide for the safe level of Roundup.

The endocrine disruptive level of Roundup found in the experiment, of 10 mg/kg bw/d, is is well above the acceptable daily intake (ADI) set for glyphosate in Europe (0.3 mg/kg bw/d) and the US (1.75 mg/kg bw/d). But this isn’t a reason to feel reassured, since with endocrine effects, low doses can be more disruptive than higher doses.

Another worrying factor is that 10 mg/kg bw/d is well below the NOAEL (no observed adverse effect level) for chronic toxicity of glyphosate: 500 mg/kg bw/d for chronic toxicity, according to the US EPA.

In other words, the level of 500 mg/kg bw/d – a massive 50 times higher than the level of Roundup found to be endocrine disruptive in the experiment – is deemed by US regulators not to cause chronic toxicity.

This experiment shows they are wrong by a long shot. They failed to see toxicity below that level because they failed to take endocrine disruptive effects from low doses into account and industry does not test for them.

Hormone disruption take place at or below ‘no adverse effects’ levels

Interestingly, the NOAEL for glyphosate in industry’s three-generation reproductive studies in rats was much lower than that for chronic toxicity – 30 mg/kg bw/day for adults and 10 mg/kg bw/day for offspring.

However the latter figures – at which no adverse effects should be apparent from glyphosate – are at the same as or higher level than the level of Roundup found to be endocrine disruptive in the new study.

These results therefore show that the reproductive processes of the rats are sensitive to low doses that are apparently not overtly toxic. This in turn suggests that the reproductive toxicity findings are due to endocrine disruptive effects.

Regulatory tests still do not include tests for endocrine disruption from low doses, in spite of the fact that scientists have known about the syndrome since the 1990s.

In the final section of the new study, the researchers discuss its implications. They note that the effects seen in the Roundup-treated rats to the Adrenocorticotropic hormone receptor (ACTH) were similar to adrenal insufficiency in humans:

“The findings that Roundup treatment down regulates endogenous ACTH, is similar to the condition known as adrenal insufficiency in humans. This condition manifests as fatigue, anorexia, sweating, anxiety, shaking, nausea, heart palpitations and weight loss. Chronic adrenal insufficiency could be fatal, if untreated.

“A progressive increase in its prevalence has been observed in humans, while a very few studies relating to xenobiotic exposure and adrenal insufficiency development have been reported. The present study describes one of the possible mechanisms of adrenal insufficiency due to Roundup and suggests more systematic studies, to investigate the area further. “

Claire Robinson of GMWatch commented: “Since no safe dose has been established for Roundup with regard to endocrine disrupting effects, it should be banned.”

 

 

The study: ‘Analysis of endocrine disruption effect of Roundup in adrenal gland of male rats‘ is by Aparamita Pandey and Medhamurthy Rudraiah, and published in Toxicology Reports 2 (2015) pp.1075-1085 on open access.

This article was originally published by GMWatch. This version has been subject to some edits and additions by The Ecologist.

From http://www.theecologist.org/News/news_round_up/2985058/roundup_may_cause_potentially_fatal_adrenal_insufficiency.html

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Adrenal insufficiency – how to spot this rare disease and how to treat it

Posted on June 6, 2015 by MaryO

adrenal-glandsAddison’s disease, or adrenal insufficiency, is a rare hormonal disorder of the adrenal glands that affects around 8,400 people in the UK.

The adrenal glands are about the size of a pea and perched on top of the kidneys, and affect the body’s production of the hormones cortisol and sometimes aldosterone.

When someone suffers from adrenal insufficiency, those glands aren’t producing a sufficient amount of these hormones. This can have a detrimental effect on someone’s health and well-being. But because the symptoms are similar to a host of other conditions, Addison’s disease can prove tough to isolate.

What to look out for

According to advice provided by the NHS, the symptoms in the early stages of Addison’s disease, which affects both men and women, are gradual and easy to misread as they’re similar to many other conditions.

People can experience severe fatigue, muscle weakness, low moods, loss of appetite, unintentional weight loss, low blood pressure, nausea, vomiting and salt craving.

“Symptoms are often misread or ignored until a relatively minor infection leads to an abnormally long convalescence, which prompts an investigation,” says Professor Wiebke Arlt from the Centre for Endocrinology, Diabetes & Metabolism at the University of Birmingham.

Life-threatening condition

If Addison’s disease is left untreated, the level of hormones produced by the adrenal gland will gradually decrease in the body. This will cause symptoms to get progressively worse and eventually lead to a potentially life-threatening situation called an adrenal, or Addisonian, crisis. Signs include severe dehydration; pale, cold, clammy skin; rapid, shallow breathing; extreme sleepiness; severe vomiting and diarrhoea. If left untreated, it can prove fatal, so the patient should be admitted to hospital as an emergency.

Back to basics

To understand the disorder, it’s important to get to grips with the basics and that means understanding what the adrenal glands are – and so to the science.

“Adrenal glands have an inner core (known as the medulla) surrounded by an outer shell (known as the cortex) ,” explains Arlt.
The inner medulla produces adrenaline, the ‘fight or flight’ stress hormone. While the absence of this does not cause the disease, the cortex is more critical.

“It produces the steroid hormones that are essential for life: cortisol and aldosterone,” he adds.

“Cortisol mobilises nutrients, enables the body to fight inflammation, stimulates the liver to produce blood sugar and also helps control the amount of water in the body. Aldosterone, meanwhile, regulates the salt and water levels, which can affect blood volume and pressure.”

Why does it happen?

The disorder occurs if the adrenal glands are destroyed, absent or unable to function and failure of the glands themselves is known as primary adrenal insufficiency.

“It’s most often caused by autoimmune disease where the body’s immune system mounts an attack against its own adrenal glands,” explains Arlt.

“However it can also be caused by infection, most importantly by tuberculosis and sometimes by both adrenal glands being surgically removed.”

The pituitary effect

Another important cause is any disease affecting the pituitary gland, which is located behind the nose at the bottom of the brain.
“The pituitary is the master gland that tells the other glands in the body what to do,” continues Arlt.

“The pituitary gland produces a hormone called ACTH (adrenocorticotropic hormone to give it its full name), which travels in the blood stream to the adrenal glands.

“Here it acts as a signal, causing the adrenal glands to produce more cortisol. If the pituitary gland stops making ACTH, [then] cortisol production by the adrenals is no longer controlled properly and a condition called secondary adrenal insufficiency arises.”

But in most cases, aldosterone is still produced, which means that people suffering from secondary adrenal insufficiency have fewer problems than those with primary adrenal insufficiency.

Determining a diagnosis

Due to the ambiguous nature of the symptoms, a Short Synacthen Test (SST) needs to be performed in order to diagnose adrenal insufficiency.

“This measures the ability of the adrenal glands to produce cortisol in response to (the pituitary hormone) ACTH,” says Arlt. “When carrying out this test, a baseline blood sample is drawn before injecting a dose of ACTH, followed by drawing a second blood sample 30 to 60 minutes later. Failing adrenal glands will not be able to produce a certain level of cortisol.”

Getting treatment

If someone has been conclusively diagnosed with adrenal insufficiency, they should receive adrenal hormone replacement therapy as advised by an endocrinologist, a doctor specialising in hormone-related diseases.

“A normal adrenal gland does not need supplements to function properly and there is no recognised medical condition called ‘adrenal fatigue’,” warns Arlt.

“Either the adrenal gland is fine and needs no treatment or there is adrenal insufficiency due to adrenal or pituitary failure.”

So if in doubt, don’t self-diagnose but book an appointment with your GP.

For more information, visit Addison’s Disease Self-Help Group (www.addisons.org.uk) or Pituitary Foundation.

From https://home.bt.com/lifestyle/wellbeing/adrenal-insufficiency-how-to-spot-this-rare-disease-and-how-to-treat-it-11363985141306

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