Allen Institute and BioMarin Collaborate to Develop Gene Therapies for Rare Brain Diseases

Rare Daily Staff

The Allen Institute and BioMarin Pharmaceutical said they will collaborate to use technologies developed at the Allen Institute to create new gene therapies aimed at rare genetic diseases of the central nervous system, which target gene expression to specific cells.

BioMarin will receive an exclusive license to each program for research, development and commercialization. The organizations did not disclose financial terms.

“This collaboration offers us great opportunities to partner with scientific leaders to develop therapies in the CNS therapeutic area,” said Lon Cardon, senior vice president and chief scientific strategy officer at BioMarin Pharmaceutical.

It is increasingly understood in the scientific research community that many central nervous system disorders affect individual brain circuits or cell types rather than the entire brain. Gene therapies are emerging as a promising approach to improving outcomes for patients with these conditions. The Allen Institute for Brain Science, a division of the Allen Institute, has developed modified adeno-associated viruses, or AAVs, that have been engineered to impact specific classes of cells in the brain.

A key component of each engineered AAV is a unique molecular enhancer, which ensures that viral gene expression is restricted to only a precise cell type relevant in a particular disease. The cell type specific enhancers enable a similar control over gene expression in central nervous system tissues from several species, strongly suggesting their potential for contributing to a new class of precision gene therapies in patients. Scientists from BioMarin and the nonprofit Allen Institute will collaborate to establish whether these novel AAVs can enable the creation of a new class of gene therapies displaying a higher level of precision to treat diseases of the central nervous system.

“The technology behind these viral tools could have incredible impact for both basic neuroscience and clinical research,” said Allan Jones, president and CEO of the Allen Institute. “On the basic research side, the biggest impact will come from the Allen Institute’s traditional model of releasing data, tools and knowledge to the public for broader scientific use, as we have with versions of these tools used in basic research. BioMarin’s industry leading expertise in gene therapy and drug development will allow for the transformation of the basic research to clinical therapy candidates.”

The licensed technology was originally developed by researchers at the Allen Institute for Brain Science toward the goal of studying and classifying individual brain cell types. The tools are built by engineering AAVs to carry genes that switch on in specific types of neurons or other cells in the brain. A key component of these engineered AAVs is a molecular “zip code” or enhancer, which ensures that gene expression is restricted only to the correct cellular address in the brain.

Neuroscientists at the Allen Institute have been using these tools to ferry fluorescent labels to the brain, lighting up single brain cell types or subclasses of brain cells under the microscope to enable better studies of individual cell types. The researchers have also shown that the same tools can often selectively label comparable cell types. The viral tools for labeling brain cell types were described in two recent publications led by research teams at the Allen Institute for Brain Science, which were published March 30, 2021 in the journals Neuron and Cell Reports.