From diabetes to DMD

Heat shock protein therapy found to have surprising potential in alternate indication

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NEW YORK—N-Gene Research Laboratories Inc. (N-Gene), adiabetes research biopharmaceutical company based in New York, recentlyannounced a new discovery centered on BGP-15, the company's lead compound.Australian scientists working in close cooperation with N-Gene researchers discoveredthat the compound, which is currently being developed as a diabetes treatment,could have potential as a novel therapy for treating Duchenne musculardystrophy (DMD). The results were recently published in Nature.
BGP-15 is a heat shock protein inducer and a co-inducer ofheat shock protein 72 (Hsp72) that causes an increase in insulin sensitivity byblocking JNK phosphorylation. The compound is currently being tested in aninternational Phase IIb study in patients with type 2 diabetes, with resultsexpected by the end of this year.
As a diabetes therapy, BGP-15 exhibits a variety ofadvantages over existing approaches, says Gabor K. Kalman, CEO of N-Gene. Itoffers a better safety profile, he says, without the cardiovascular issues,water retention or liver toxicity often seen in some diabetes drugs. Inaddition, Kalman adds that as the compound is "basically a cytoprotectiveagent," it could have been developed independently from diabetes as acardioprotective drug as well.
DMD is a form of muscular dystrophy that gets worse rapidly.Caused by a defective gene for dystrophin, a protein found in the muscles, itmanifests itself in muscle weakness, which begins in the legs and pelvis. Thecondition occurs in roughly 1 out of every 3,500 male infants. There is no cureor any effective therapies for DMD. In the recently published work, BGP-15 wastested in animal models of DMD and was found to not only make a pivotal proteinfunctional again, reducing muscle damage, but to also increase the strength,endurance and lifespan of the animal models.
"We believe this publication reinforces the expectation thatN-Gene's platform technology, based on stress-response regulation, willeventually result in the emergence of a novel drug class with diversetherapeutic directions," Dr. Peter Literati, co-founder and chief scientificofficer of N-Gene, said in a press release.
BGP-15's potential in treating DMD came as a surprise, saysKalman. The company's co-chief scientific officer, Dr. Mark Febbraio, isalso the head of the Cellular and Molecular Metabolism Laboratory and directorof Basic Science in the Division of Metabolism and Obesity at the Baker IDIHeart and Diabetes Research Institute. Febbraio has a working relationship withProf. Gordon Lynch, head of the Department of Physiology at the University ofMelbourne, says Kalman, and the two discussed BGP-15's potential in treatingmuscular dystrophy, which then led to the animal studies. Lynch led theresearch, which was conducted by Dr. Stefan Gehrig of the Basic and ClinicalMyology Laboratory in the University of Melbourne's Department of Physiology incollaboration with Febbraio and his team at Baker IDI Heart and DiabetesInstitute.
It was noted in the paper that the results "provide evidencethat increasing the expression of Hsp72 in muscle (through the administrationof BGP-15) has significant therapeutic potential for DMD and relatedconditions, either as a self-contained therapy or as an adjuvant with otherpotential treatments, including gene, cell and pharmacological therapies." Anews release from the Department of Medicine, Dentistry and Health Sciences onthe University of Melbourne's website noted that "upregulating heat shockprotein 72 in skeletal muscles of mice with severe muscular dystrophy, improvedmuscle strength, slowed the disease progression and increased lifespan by morethan 20 percent."
Kalman says the company believes heat shock proteins couldhave potential in several other indications as well.
"We believe that there may be a part in Parkinsonism, inAlzheimer's and other neurodegenerative and metabolic diseases, in polycysticovarian syndrome and muscle dystrophy," says Kalman. "So quite a wide range oftherapies may benefit from heat shock protein science."
He adds that "it is yet a dilemma" whether they will pursuethe muscular dystrophy avenue with the compound, as the diabetes indication isboth clearer and more advanced in development. According to Literati, thecompany will remain focused on advancing the compound within the diabetesindication, "but we look forward to seeking partners with which to advance thistechnology and realize its potential in the treatment of DMD as well as manyother disease indications."
"I believe that quite a lot of companies are looking forindications such as DMD, and we already had one tentative interest from a Big Pharma partner, and I believe that because this is such a unique result, whatwe could demonstrate, that it's really gearing interest or it will gearinterest from Big Pharma," says Kalman. 

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