Pharmacy lecture held on TDP-43 protein, link to ALS

On Oct. 29, the Department of Pharmaceutical Sciences held a seminar lead by Dr. Allen B. Reitz titled “Characterization of small-molecule TDP-43 ligands TDP-43 for the treatment of ALS and related disorders.”

Reitz is a graduate of the University of Pennsylvania and received his graduate degree from the University of California San Diego. He also worked for Johnson and Johnson for 26 years.

He has worked over 35 years as a medicinal chemist leading research efforts in the areas of diseases of the central nervous system.

Reitz believes that the background he had in business helped him get to where he is now but calls himself a “chemist by training.”

He came to campus to discuss the research being done at the Fox Chase Chemical Diversity Center which he founded in 2008 outside of Philadelphia. The center is primarily focused on chemistry and pharmacology based on early drug discovery.

The primary focus of the seminar was the TDP-43, which is a transactive response DNA-binding protein. This protein is used to bind DNA and RNA and regulates some of the RNA processing.

Fox Chase Chemical and Diversity Center is studying this protein as it links to numerous diseases such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) as well as Chronic Traumatic Encephalopathy (CTE) and Alzheimer’s Disease.

Allie Shulskie, a sophomore pharmacy major, found the discussion and study of these diseases particularly important.

“So many of us know someone who suffers from these diseases and hearing about the progress they are making is really reassuring.”

‘It’s also interesting to hear about drug discovery. We’ve all heard of the drugs, but most people don’t understand where they come from or how they’re developed,” said Shulskie.

Last year was the most productive year ever for approval by the FDA of new molecular entities into therapies. In 2018 there were 59 approvals compared to 2017 and 2016 which had 46 and 22 drugs, respectively.

Reitz discussed a new drug, Troriluzole, which passed to clinical trials after 15 months and 11 days when drug acceptance usually takes much longer.

He explained that the quick development of Troriluzole is a result of a better drug discovery process which starts from scientific literature and continues to clinical trials. This drug is now being tested in five different trials, one of which includes 400 people suffering from ALS.

Although his science background is important to the research he is doing, Reitz credits more than just his education for his successes.

He acknowledged his research team throughout the seminar.

“The reason I can do what I do is the people. Teams aren’t part of it, they’re all of it. How people work together, getting diversity in your team, both are really important,” said Reitz.

This team mindset was important when Reitz worked with the University of Arizona analyzing the TDP-43 protein in fruit fly life cycles. Dr. Reitz explained that fruit flies turn during their larval state which generally takes about 13 seconds.

However, when adding the TDP-43 protein, this turn happens in 25 seconds.

This study relates to ALS which affects patients’ motor skills. Understanding how TDP-43 affects fruit flies can translate into how TDP-43 affects humans. By studying these fruit flies, researchers will develop hypotheses about ALS in humans.

Reitz thinks that these new hypotheses are a start to new scientific discoveries.

When asked for advice to give to students he said, “There is no better time than now to be a scientist, with the 59 new drugs approved last year, there is no better time than now to try to understand the molecular basis of disease and toxicology.”

However, Reitz understands some fears students have about entering the job market.

“Getting a job is very competitive and you have to be diversified and broad-based,” he said.

His overall advice was to take science classes. He explains that although the topics are complicated, students, as well as the general public, should be encouraged to learn about them.