Beta-O2’s ßAir Bio-artificial Adrenal Device Shows Potential to Treat Adrenocortical Insufficiency and Other Stress-related Disorders

ROSH HAAYIN, Israel, February 19, 2015 /PRNewswire/ —

Beta-O2 announced today the results of a series of pre-clinical studies demonstrating that the company’s ßAir Bio-artificial Adrenal device could offer a treatment for adrenocortical insufficiency and other stress-related disorders. The results are published in the current issue of the Proceedings of the National Academy of Sciences of the United States of America (PNAS). PNAS is one of the world’s most-cited and comprehensive multidisciplinary scientific journals, publishing more than 3,800 research papers annually.

The article, titled “Transplantation of bovine adrenocortical encapsulated in alginate can be viewed here .

The studies cited in the article were led by Professor Stefan Bornstein and Dr. Mariya Balyura at University Hospital Carl Gustav Carus Dresden.

Professor Bornstein said, “The Bio-artificial Adrenal supersedes an immunosuppression completely. The donor cells will be protected against the immune system responses of the patient. The system lets hormones pass the half-permeable walls into the body of the receiver. Our vision is that people in the future may even receive adrenal cells from another species, as, for example, from the pig. The device creates the biotechnical conditions for it.”

Professor Bornstein continued, “I am convinced that Beta-O2’s ßAir Bio-artificial Adrenal device will revolutionize the therapy of adrenocortical insufficiency. Many more patients could benefit from transplantation because the recipients wouldn’t need any immunosuppressive drugs, at all.”

ßAir is an implantable device that provides immune protection and optimal living conditions for cells implanted within it. It has thus far proven successful in providing a viable environment for islets of Langerhans or beta cells, to thrive and naturally produce insulin on demand, a necessary function missing in people with type 1 diabetes. The product for type 1 diabetes is called the ‘ßAir Bio-artificial Pancreas’. Three patients are currently implanted with the ßAir Bio-artificial Pancreas as part of an ongoing clinical study in Sweden.

“The news today indicates that the same immune protection system being used to treat type 1 diabetes patients in the clinical trial in Sweden, also appears to work well for other types of functional cells, such as adrenal cells. We found that when placed in the ßAir, the life span of the adrenal cells significantly increased. The capacity of the adrenal cells for stable, long-term basal hormone release significantly improved as well, as did their response to various stimulating hormones. Additionally, as described in the PNAS article, we learned that ßAir has xeno transplantation or cross species capabilities. For example, using the ßAir, pig adrenal cells can be transplanted into a living being other than a pig and still remain healthy and function properly,” said Dr. Dan J. Gelvan, chairman of the board of Beta-O2.

Dr. Gelvan continued, “What all this means is that transplantation of a ‘ßAir Bio-artificial Adrenal’ with cells from another species could prove to be a treatment option for patients with adrenocortical insufficiency and other stress-related disorders. This is important because current treatment options for adrenal insufficiency are limited and have unpleasant side effects. The study findings reported in the PNAS article are also significant as they offer a sneak preview of the huge potential of ßAIR. If it can provide a viable environment for many different types of cells, then ultimately it may be prove to afford an effective treatment, if not a cure, for a long list of illnesses.”

About Beta-O2 Technologies Ltd.

Beta-O2 Technologies Ltd. is a biomedical company developing a proprietary implantable bioreactor, the ßAir. The company’s flagship product is called the ßAir Bio-artificial Pancreas. It is in development as a treatment and potential cure for type 1 diabetes (T1D). ßAir was first designed to address the main problems of the otherwise successful procedures in which islets of Langerhans (i.e. pancreatic endocrine cells) are transplanted in diabetic patients, such as the need for life-long immunosuppressive pharmacological treatment and limited functionality of the transplanted islets over time due to an insufficient oxygen supply. The company’s second pipeline product is the ßAir Bio-artificial Adrenal for the treatment of adrenocortical insufficiency and other stress-related disorders. This product is currently at the pre-clinical stage of development. Beta-O2 investors include Aurum Ventures, Sherpa Innoventures, SCP Vitalife Partners, Pitango Venture Capital and Saints Capital.

For more information, please visit http://www.beta-o2.com .

Press contact:
Marjie Hadad
MH Communications
+972-54-536-5220
marjie@netvision.net.il

 

SOURCE Beta-O2 Technologies Ltd

Higher Doses of ‘Abortion Pill’ Safe in Cushing’s?

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

LAS VEGAS — Higher doses of mifepristone for Cushing’s disease (Korlym) weren’t associated with increases in serious adverse events, researchers reported here.

Korlym is a glucocorticoid receptor antagonist better known as RU-486, or the “abortion pill.” It was approved for treating hyperglycemia associated with Cushing’s disease in 2012.

In an analysis of data from the SEISMIC trial, Dat Nguyen, MD, and colleagues found that similar percentages of patients had serious adverse events across all doses of the drug, reported.

They also reported at the American Association of Clinical Endocrinologists meeting here, that the proportion of the four most common adverse events — headache, fatigue, nausea, and hypokalemia — fell off after 10 weeks of the 24-week trial.

“Recent prescription data indicate that many physicians are not titrating beyond 300 mg per day, potentially limiting patients’ clinical response,” the researchers said.

The 2012 approval was based on the SEISMIC study, which followed 50 Cushing’s disease patients over 24-weeks in an open-label format. It found that daily doses improved blood sugar control and reduced insulin requirements.

Clinicians participating in the trial were told they could titrate beyond the starting dose of 300 mg a day. To look at the relationship between dose and safety, as well as response, Nguyen and colleagues looked at data on 40 of the patients who responded to therapy.

Most of them (90%) were taking at least 600 mg a day, 68% were taking at least 900 mg per day, and 44% took 1,200 mg daily.

Most of the responders (85%) had their initial clinical response at a dose of at least 600 mg daily.

Overall, there were 26 serious adverse events:

  • 10 at the 300 mg dose
  • 8 at the 600 mg dose
  • 3 at the 900 mg dose
  • 3 at the 1200 mg dose
  • 2 while off drug

 

When the researchers adjusted for the number of patients who had ever reached a given dose, the frequency of serious adverse events was similar across doses:

  • 10% of patients at 300 mg
  • 16% of patients at 600 mg
  • 15% of patients at 900 mg
  • 14% of patients at 1200 mg

 

The four most common adverse events decreased after week 10 – although that tracked an increase in dose (mean 588 mg/day before week 10 versus 895 mg/day thereafter).

Nguyen and colleagues concluded that higher doses of mifepristone weren’t associated with increases in serious adverse events or in the most common adverse events – and that better response was seen with higher doses.

Korlym was developed by Corcept Therapeutics of Menlo Park, Calif., as an orphan drug given that it is is believed only 5,000 patients are eligible for treatment. That gave the company 7 years of exclusive rights to market the agent for Cushing’s disease.

The label limits the drug’s indication to patients with endogenous Cushing’s disease who have type 2 diabetes or glucose intolerance and aren’t candidates for surgery, or failed to respond to surgical intervention.

The drug doesn’t reduce cortisol production but prevents it from binding to its receptor – an action separate from its blockade of the progesterone receptor, which makes it an effective agent in abortion.

Since the daily doses are in the same range as those used to induce abortion, the drug is contraindicated in pregnant women. It also carries a boxed warning that the drug will terminate a pregnancy.

From http://www.medpagetoday.com/MeetingCoverage/AACE/45790

Skeletal Maturation in Children With Cushing’s Syndrome is Not Consistently Delayed

Skeletal maturation in children with cushing syndrome is not consistently delayed: The role of corticotropin, obesity, and steroid hormones, and the effect of surgical cure.

J Pediatr. 2014 Jan 9. pii: S0022-3476(13)01500-X. doi: 10.1016/j.jpeds.2013.11.065. [Epub ahead of print]

The Journal of Pediatrics, 01/22/2014 Clinical Article

Lodish MB, et al. – The aim of this study is to assess skeletal maturity by measuring bone age (BA) in children with Cushing syndrome (CS) before and 1–year after transsphenoidal surgery or adrenalectomy, and to correlate BA with hormone levels and other measurements. Contrary to common belief, endogenous CS in children appears to be associated with normal or even advanced skeletal maturation. When present, BA advancement in CS is related to obesity, insulin resistance, and elevated adrenal androgen levels and aromatization. This finding may have significant implications for treatment decisions and final height predictions in these children.

Methods

  • This case series conducted at the National Institutes of Health Clinical Center included 93 children with Cushing disease (CD) (43 females; mean age, 12.3 ± 2.9 years) and 31 children with adrenocorticotropic hormone–independent CS (AICS) (22 females, mean age 10.3 ± 4.5 years).
  • BA was obtained before surgery and at follow-up.
  • Outcome measures were comparison of BA in CD vs AICS and analysis of the effects of hypercortisolism, insulin excess, body mass index, and androgen excess on BA.

Results

  • Twenty-six of the 124 children (21.0%) had advanced BA, compared with the expected general population prevalence of 2.5% (P < .0001). Only 4 of 124 (3.2%) had delayed BA.
  • The majority of children (76%) had normal BA.
  • The average BA z-score was similar in the children with CD and those with AICS (0.6 ± 1.4 vs 0.5 ± 1.8; P = .8865).
  • Body mass index SDS and normalized values of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androsteonedione, estradiol, and testosterone were all significantly higher in the children with advanced BA vs those with normal or delayed BA.
  • Fifty-nine children who remained in remission from CD had follow-up BA 1.2 ± 0.3 years after transsphenoidal surgery, demonstrating decreased BA z-score (1.0 ± 1.6 vs 0.3 ± 1.4; P < .0001).

From http://www.ncbi.nlm.nih.gov/pubmed/24412141

Is Diabetes in Cushing’s Syndrome a Consequence of Hypercortisolism?

Eur J Endocrinol. 2013 Nov 19. [Epub ahead of print]

Is Diabetes in Cushing syndrome only a consequence of hypercortisolism?

Source

C Giordano, Dipartimento di Medicina Interna e Specialistica (Di.Bi.Mi.S) Sezione di Endocrinologia e Malattie del Metabolismo, University of Palermo, Palermo, Italy.

Abstract

OBJECTIVE:

Diabetes mellitus (DM) is one of the most frequent complications of Cushing syndrome (CS). Aim of the study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients.

DESIGN:

Cross-sectional study on 140 patients with CS.

METHODS:

113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 yr) and 27 men (19 with pituitary disease and 8 with adrenal disease, aged 38.1±20.01 yr) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes) and diabetes (CS/DM).

RESULTS:

71 patients belonged to CS/NGT (49.3%), 26 (18.5%) to CS/prediabetes and 43 (30.8%) to CS/DM. Significant increasing trends in the prevalence of family history of diabetes (p<0.001), metabolic syndrome (p<0.001), age (p<0.001) and waist circumference (p=0.043) and decreasing trends in HOMAβ (p<0.001)and Oral Dispositional Index (DIo) (p<0.002) were observed among the groups. No significant trend in fasting insulin, AUC INS, ISI-Matsuda and VAI was detected.

CONCLUSIONS:

Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in the natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of patients at high risk for metabolic complications.

PMID:
24255133
[PubMed – as supplied by publisher]
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