Nearly nine years ago Jeanne Loring and her colleagues at Scripps Research debuted a test that leveraged advances in genomics and data science to determine, without testing in animals, whether human stem cells were “pluripotent,” or able to become any type of cell in the body.
Being able to prove that has become increasingly important as scientists look to induced pluripotent stem cells (iPSCs)—mature, specialized cells that have been reprogrammed as immature cells, regaining the capability of becoming any type of cell—as material for new regenerative medicines.
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Now Loring and Andres Bratt-Leal, who joined her lab in 2012 as a post-doctoral researcher, have founded a biotech that combines stem cell biology and genomics know-how to advance a potential cell therapy for Parkinson’s disease.
The startup announced Thursday it raised a seed round of $6.5 million to support its work. Aspen’s lead drug candidate, which is in preclinical testing, is intended to replace neurons in the brains of people with the disease, which causes those cells to become damaged or die.
When people with Parkinson’s disease lose neurons, they also lose a chemical messenger the cells produce, called dopamine. Without dopamine, communication between nerve cells falters, which leads to the debilitating motor problems that characterize the disease. Existing Parkinson’s drugs aim to alter dopamine levels. Aspen, however, wants to fix the upstream problem that leads to those lowered levels by reconstructing patients’ damaged neural networks.
The cell therapy would involve harvesting patients’ own living cells through a skin biopsy, reprogramming them to immature cells, or iPSCs, then further engineering them to become predisposed to mature into neurons. Once enough of those cells have been grown in the lab, those neuron precursor cells would be delivered directly to the brain.
Using a patient’s own cells avoids the dangerous immune system reactions that can occur when donor cells are used in such therapies, and obviates the need for immunosuppression drugs. Two cell therapies that use genetic engineering have been approved by the FDA, both of which take and tweak patients’ T cells into treatments for cancer. Stem cell transplants have been used to treat some cancers.
Aspen worked to ensure the company could ably manufacture a so-called autologous replacement cell therapy, or one from a patient’s one cells, by improving the process of differentiating iPSCs into dopamine neurons, Loring says. And the group developed another predictive genomic-based test, similar to the effort Loring spearheaded nearly a decade ago to determine whether cells were pluripotent, that can detect which iPSCs are destined to become neurons.
“(Bratt-Leal) put his biological engineering expertise into coming up with a way that was reproducible, that we would get the same cells no matter who we got the original cells from,” she says.
The company plans to test the therapy in patients that they determine, through genomic testing, have the most common form of Parkinson’s, which is referred to as sporadic and arises without a clear genetic predisposition. It also has a second treatment in the works that it intends to develop for patients with familial forms of the disease, and uses a gene editing tool—yet to be selected—to alter their stem cells during the reprogramming process.
Howard Federoff, who was most recently vice chancellor for health affairs and CEO of the UC Irvine Health system, is Aspen’s CEO. Federoff says he has “come to believe that Parkinson’s patients need more than just to stabilize their disease… They need to turn the clock back.”
Many companies are working on drugs to treat Parkinson’s, but most are meant to manage symptoms rather than reverse the disease. Levodopa, which supplants missing dopamine, is used widely, but it can cause side effects, including involuntary movement called dyskinesia; and, as the disease progresses, the drug eventually stops working between doses.
Aspen claims it is the only company working toward an autologous neuron replacement. The company, however, will need to raise a Series A round to move its drug candidates through Phase 2 proof-of-concept trials, Loring says.
The company raised its seed round from a group of investors including Domain Associates, Alexandria Venture Investments, Arch Venture Partners, Axon Ventures, OrbiMed, and Section 32. Initially, it was financed through grants from Summit for Stem Cell, a San Diego-based nonprofit.