LA BioMed News

Phoenix Nest and LA BioMed Receive Over $1.7 million to Develop Treatments for Devastating Childhood Disease
Tuesday, May 31, 2016

The National Institute of Neurological Disorders and Stroke recently awarded over $1.7 million in grant funding to Phoenix Nest, Inc. to continue its partnership with the Los Angeles Biomedical Institute (LA BioMed) to research the development of therapies for treating different forms of a devastating inherited genetic disorder, Sanfilippo disease, also known as MPS III.

MPS III disease is a progressive neurological disorder that is generally diagnosed in childhood and can lead to premature death. The new grants are for therapies to combat devastating brain disease due to MPS III types B and D.

Funding for work in MPS IIID is for recombinant enzyme therapy and is a Phase 2 Small Business Technology Transfer (STTR) award, following a successful $223,102 Phase 1 award. Phoenix Nest and LA BioMed were also awarded a Phase 1 STTR grant to develop a novel stem cell therapy for MPS IIIB syndrome. Both treatments have the potential to completely transform the care of children with MPS III disease, as no approved treatments currently exist for any type.

“We are pleased to continue our partnership with Phoenix Nest, Inc. in this important research to help children living with MPS III B and D. After promising results obtained in our first preclinical studies for an enzyme replacement for MPS IIID, we will next look at efficacy in a disease model with a goal of moving towards the clinic as quickly as we can,” said Patricia I. Dickson, MD, LA BioMed lead researcher and director of the institute’s MPS Research Laboratory.

Dr. Dickson has specific expertise in the development of intrathecal enzyme replacement therapies for treating MPS by replacing the missing enzyme through the patients’ spinal fluid.

“We are very grateful to the National Institute of Neurological Disorders and Stroke for continuing to fund this project to find more effective therapies for MPS IIID, which is so debilitating to the patients and causes enormous stress for the families involved,” said Sean Ekins, PhD, chief executive officer of Phoenix Nest, Inc. “The additional funding will be used to manufacture an enzyme for further testing. The research is seeking to develop a therapy that will limit or reverse the neurological damage caused by MPS IIID by delivering an enzyme, recombinant human alpha-N-acetylglucosamine-6-sulfatase (rhGNS), intrathecally to effectively treat the underlying causes of the neurologic symptoms of MPS IIID.”

The National Institute of Neurological Disorders and Stroke also provided funding for development of a treatment for MPS IIIB. “This represents a novel approach to use stem cells to make the enzyme alpha-N-acetylglucosaminidase that is needed to achieve therapeutic benefit,” said Dr. Dickson.

“Phoenix Nest, Inc. is solely focused on Sanfilippo syndrome, and we are honored to continue collaborating with Drs. Dickson, Tsui-Fen Chou, Michelina Iacovino and their teams so that we can develop multiple treatments for MPS IIIB and MPS IIID,” said Dr. Ekins.

Sodium Bicarbonate Treatments Could Prevent Deadly Fungal Infections In Patients with Diabetic Ketoacidosis
Monday, May 9, 2016

New Study Identifies Processes Leading to Mucormycosis Infections

Patients with diabetic ketoacidosis (DKA) face a much higher risk of succumbing to a deadly fungal infection, known as mucormycosis, than healthy patients. A new study suggests a simple treatment of sodium bicarbonate, or baking soda, could prevent the spread of mucormycosis in patients with DKA. 

The study, published today in The Journal of Clinical Investigation, found sodium bicarbonate reversed the effects that promoted the spread of mucormycosis in DKA, a life-threatening condition that can affect people with diabetes. DKA occurs when the body cannot use sugar, or glucose, as a fuel source because there is no insulin or not enough insulin. Fat is used for fuel instead, triggering acids, called ketones, to accumulate in the body. In high levels, ketones are poisonous and can lead to a diabetic coma and death.

“The current guidelines for correcting acidosis of DKA patients doesn’t indicate using sodium bicarbonate until the acidosis is severe,” said Ashraf S. Ibrahim, PhD, an LA BioMed lead researcher and corresponding author of the study. “Our data strongly suggest that DKA patients suspected of having mucormycosis would benefit from adding sodium bicarbonate to the treatment regimen — regardless of whether they have severe acidosis or not — because sodium bicarbonate is likely to halt the growth of the fungus.”

The researchers identified the processes in DKA that promoted the growth of mucormycosis and suppressed the effect of the phagocytes, which are cells within the body capable of engulfing and absorbing invading microorganisms. They found fungal cell surface proteins, CotH, bind to the mammalian cell receptor, GRP78, during the invasion of host tissues.

In DKA patients, they also identified other host factors – including elevated glucose, iron and ketone bodies –that enhanced the expression of both the fungal and mammalian cell receptors in a way that promoted enhanced invasion and damage of host tissues.

In addition, the study noted that acidosis seen in DKA exerts an indirect effect by liberating iron from transferrin, which in turn augmented the expression of GRP78 and CotH, suppressed phagocyte function and enhanced growth of the fungus.

Collectively, these effects promoted rapid infection and progression of mucormycosis. Using disease models, the researchers found sodium bicarbonate reversed many of these effects and helped defeat the mucormycosis infection.

Their finding of elevated iron levels also suggested that reducing the amount of iron by the use of iron chelation, in conjunction with sodium bicarbonate treatment, would help prevent mucormycosis infections in patients with DKA. The researchers also noted that further studies are needed in well-designed clinical trials involving patients with DKA and mucormycosis infections.

To see the full text of the study, please click here.

Other LA BioMed researchers involved in the study were: Teclegiorgis Gebremariam, Lin Lin, Mingfu Liu, Samuel French, John E. Edwards Jr. and Scott G. Filler. Dimitrios P. Kontoyiannis from the Department of Infectious  Diseases, Infection Control and Employee Health, The University of Texas M D Anderson

Cancer Center, Houston, TX, also participated in the study. This work was supported by Public Health Service grants R01 AI063503 and 1R41 AI115907-01 677. Individual researchers were supported by Grant Nos. 678 UL1TR000124, R01 AI054928 and R01 AI063382.

Tuesday, May 31, 2016

NEWS

Phoenix Nest and LA BioMed Receive Over $1.7 million to Develop Treatments for Devastating Childhood Disease

Monday, May 9, 2016

NEWS

Sodium Bicarbonate Treatments Could Prevent Deadly Fungal Infections In Patients with Diabetic Ketoacidosis

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