PJ Brooks, NIH

Philip John (P.J.) Brooks PhD

Program Director, Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health

Philip John (P.J.) Brooks joined the NCATS Office of Rare Diseases Research as a program director in August 2018. Prior to that time, he was in the NCATS Division of Clinical Innovation, where he was the lead program director for the Clinical and Translational Science Awards (CTSA) Program Collaborative Innovation Awards, designed to fund projects that will result in novel and creative approaches to overcoming roadblocks in translational science (PAR-18-244 and PAR-18-245). Brooks represents NCATS on the Trans-NIH Microbiome Working Group and Gene Therapy Working Groups. He is also the Working Group Coordinator for the NIH Common Fund program on Somatic Cell Genome Editing.

TRNDS Speaker Spotlight

Why are you participating in TRNDS 2019?

BROOKS: My Ph.D. is in neuroscience, and finding better and more efficient ways to develop treatments for neurologic diseases, especially rare neurologic diseases, is something I care deeply about.

What do you see as the biggest opportunities for accelerating therapeutic development in the 21st century?

BROOKS: Moving beyond the traditional “one disease at a time” framework to platform approaches. This can greatly increase the number of rare disease patients in clinical trials, especially those with diseases that are so rare that they will have little or no commercial interest. Examples include gene therapy, where a single vector can be used to treat multiple diseases by swapping the therapeutic payload; or gene editing, where there is the potential to use a single biologic (e.g. Cas9 or Cas9 -derived base editors) to treat multiple diseases by changing the sequence of the guide RNA.

Another platform is oligonucleotide therapeutics, where a given backbone chemistry may be considered as a class, which could streamline the regulatory process for new disease indications. In the rare disease space, grouping rare disease patients according to underlying molecular etiology (abnormal splicing disease, premature stop codon disease, misfolded protein disease, Tau-opathy etc.) could dramatically accelerate clinical trial start up. This approach is analogous to the genomically driven basket trials, which are state of the art in oncology, and have led to drug approvals by FDA.

How is the increasing use of modern technologies changing the field of clinical research?

BROOKS: In addition to scientific technologies described above, another opportunity is wearable devices for clinical outcomes, and the use of telemedicine for rare disease clinical trials. Especially for patients with neurologic diseases, and diseases that impact patient’s behavior, observations of patients in the home via telemedicine makes much more sense than having them travel long distances for evaluation.

What is a critical topic you’d like to see discussed at TRNDS 2019?

BROOKS: How can we expand newborn screening for rare genetic diseases in the USA, in light of the potential of gene therapy and gene editing to treat multiple rare diseases?

What challenges lie ahead in the rare disease space?

BROOKS: Technologies such as gene therapy and gene editing have the potential for the treatment of many rare diseases. A major roadblock however is diagnosis. The rare disease diagnostic odyssey remains an unfortunate reality for many patients. Greatly expanded newborn screening could address this problem, but the current reality is a cruel Catch-22: For a new disease to become eligible for NBS, there should be an effective treatment. But for neurodegenerative disease, the best way to demonstrate efficacy are studies of presymptomatic patients. Without NBS, by definition the vast majority of patients will be symptomatic. Therefore, a fundamental reconsideration of how we do NBS in the USA is essential.