Categories
Health & Medicine Mind & Brain Researcher news SMU In The News

Dallas Business Journal: Firm is out to prevent neuron loss

Investigators at SMU and the University of Texas at Dallas have discovered a family of small molecules that shows promise in protecting brain cells against nerve-degenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s. SMU’s work is led by Chemistry Department Professor Edward R. Biehl.

Health care journalist Bill Hethcock covered the research for The Dallas Business Journal. Hethcock’s Feb. 25 article “Firm is out to prevent neuron loss” details how Dallas-based startup EncephRx Inc. was granted worldwide license to develop the jointly owned compounds.

EXCERPT:

By Bill Hethcock
Dallas Business Journal

Dallas-based biotech startup EncephRx Inc. is working with researchers at the University of Texas at Dallas and Southern Methodist University to develop treatments for Huntington’s, Parkinson’s and Alzheimer’s diseases. Already, there have been signs of promise in animal testing. The company is seeking $1 million in grants and private equity to begin pre-clinical testing in the next year.

The goal is to develop and commercialize treatments that prevent the progressive loss of neurons that characterize the diseases, said Aaron Heifetz, CEO of EncephRx. Available medications attempt to relieve symptoms, but don’t prevent neuron loss and disease progression, he said.

DBJ subscribers can read the full story

Categories
Culture, Society & Family Health & Medicine Mind & Brain

Novel compounds show early promise in treatment of Parkinson’s, Huntington’s, Alzheimer’s

Success with human trials could lead to new drugs to halt progression of nerve-degenerative diseases

Investigators at Southern Methodist University and The University of Texas at Dallas have discovered a family of small molecules that shows promise in protecting brain cells against nerve-degenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s, which afflict millions.

Dallas-based startup EncephRx, Inc. was granted the worldwide license to the jointly owned compounds. A biotechnology and therapeutics company, EncephRx will develop drug therapies based on the new class of compounds as a pharmaceutical for preventing nerve-cell damage, delaying onset of degenerative nerve disease and improving symptoms.

Treatments currently in use don’t stop or reverse degenerative nerve diseases, but instead only alleviate symptoms, sometimes with severe side effects. If proved effective and nontoxic in humans, EncephRx’s small-molecule pharmaceuticals would be the first therapeutic tools able to stop affected brain cells from dying.

“Our compounds protect against neurodegeneration in mice,” said synthetic organic chemist Edward R. Biehl, the SMU Department of Chemistry professor who led development of the compounds at SMU. “Given successful development of the compounds into drug therapies, they would serve as an effective treatment for patients with degenerative brain diseases.”

EncephRx initially will focus its development and testing efforts toward Huntington’s disease and potentially will have medications ready for human trials in two years, said Aaron Heifetz, CEO at EncephRx.

Compounds developed by SMU and UTD collaboration
Biehl developed the compounds in collaboration with UT Dallas biology professor Santosh R. D’Mello, whose laboratory has been studying the process of neurodegeneration for several years.

“Additional research needs to be done, but these compounds have the potential for stopping or slowing the relentless loss of brain cells in diseases such as Alzheimer’s and Parkinson’s,” said D’Mello, professor of molecular and cell biology at UT Dallas, with a joint appointment in the School of Brain and Behavioral Science. “The protective effect that they display in tissue culture and animal models of neurodegenerative disease provides strong evidence of their promise as drugs to treat neurodegenerative disorders.”

Millions are suffering, particularly the elderly
Parkinson’s, Huntington’s and Alzheimer’s are disorders of the central nervous system marked by abnormal and excessive loss of neurons in a part of the mid-brain, say the researchers.

The diseases steadily erode motor skills, including speech and the ability to walk, cause tremors, slowed movement, stooped posture, memory loss and mood and behavior problems.

The risk of developing a degenerative nerve disease increases with age. These diseases affect more than 5 million Americans.

Novel compounds effectively proved protective in initial studies
One member of a class of heterocyclic organic compounds, the synthetic chemicals developed and tested by SMU and UT Dallas scientists, was shown to be highly protective of neurons in tissue culture models and effective against neurodegeneration in animal models.

The most promising lead compound, designated HSB-13, was tested in Huntington’s disease animal models. It not only reduced degeneration in a part of the forebrain but also improved behavioral performance while proving nontoxic. The compound also was efficacious in a commonly used fly model of Alzheimer’s disease.

“These preliminary tests demonstrated that the compound was an extremely potent neuroprotective agent,” Biehl said.

The findings were published in the article “Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration,” which appeared in the Journal of Neuroscience Research. The National Institutes of Health and the Defense Advanced Research Projects Agency funded the project.

The SMU and UT Dallas researchers developed and tested more than 100 compounds for neuroprotective efficacy and toxicity over the course of four years before making the discovery in 2007.

Interinstitutional partnership with EncephRx
SMU researchers will assist EncephRx in optimizing the primary compound, and the UT Dallas team will support testing and analysis.

“While discovery of the compounds is a major accomplishment, many hurdles remain,” Biehl said.

EncephRx is a university spinout formed to develop and commercialize the compounds. Its management team has proven success in all facets of drug development and has developed more than a dozen chemical compounds.

Aaron Heifetz, president and chief executive officer of EncephRx, Inc., said, “We believe this library of novel neuroprotective compounds will prove an important step in the effort to improve the health for patients with neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease and Parkinson’s disease.”

Chris Jeffers, managing partner of FirstStage Bioventures, the parent company of EncephRx, added, “FirstStage is very excited about this technology and looks forward to helping EncephRx quickly move these compounds into the clinic.”

SMU has an uplink facility on campus for live TV, radio or online interviews. To speak with Dr. Biehl or Dr. D’Mello or to book them in the SMU studio, call SMU News & Communications at 214-768-7650 or UT Dallas Office of Media Relations at 972-883-4321.

SMU is a private university in Dallas where nearly 11,000 students benefit from the national opportunities and international reach of SMU’s seven degree-granting schools. For more information see www.smu.edu.

Categories
Health & Medicine Mind & Brain

Protecting brain’s neurons could halt Alzheimer’s, Parkinson’s

Researchers at Southern Methodist University and The University of Texas at Dallas have identified a group of chemical compounds that slows the degeneration of neurons, a condition that causes such common diseases of old age as Alzheimer’s, Parkinson’s and amyotropic lateral sclerosis.

SMU Chemistry Professor Edward R. Biehl and UTD Biology Professor Santosh R. D’Mello teamed to test 45 chemical compounds. Four were found to be the most potent protectors of brain cells, or neurons.

Biehl%2CEd%20lab.jpg

Their findings were published in the November 2008 issue of “Experimental Biology and Medicine.”

The synthesized chemicals, called “substituted indolin-2-one compounds,” are derivatives of another compound called GW5074 that was shown to prevent neurodegeneration in a past report published by the D’Mello lab.

While effective at protecting neurons from decay or death, GW5074 is toxic to cells at slightly elevated doses, which makes it unsuitable for clinical testing in patients. The newly identified, second generation compounds maintain the protective feature of GW5074 but are not toxic, even at very high doses, and hold promise in halting the steady march of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

“Sadly, neurodegenerative diseases are a challenge for our elderly population,” D’Mello said. “People are living longer and are more impacted by diseases like Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis than ever before, which means we need to aggressively look for drugs that treat diseases. But most exciting now are our efforts to stop the effects of brain disease right in its tracks. Although the newly discovered compounds have only been tested in cultured neurons and mice, they do offer hope.”

The most common cause of neurodegenerative disease is aging. Current medications only alleviate the symptoms but do not affect the underlying cause, which is degeneration of neurons. The identification of compounds that inhibit neuronal death is thus of urgent and critical importance.

The new compounds may offer doctors an option beyond just treating the symptoms of neurodegenerative diseases. The development isn’t a cure, but doctors may be able to one day use compounds that stop cell death in combination with currently existing drugs that battle the symptoms of brain diseases. The combination of stopping the disease in its tracks while treating disease symptoms can offer hope to people suffering and the families impacted by these diseases.

Related links:
Edward Biehl
Santosh D’Mello
SMU Department of Chemistry
Dedman College of Humanities and Sciences