When a resupply mission lifts off in August bound for the International Space Station, it will be carrying an important cargo for researchers studying Parkinson’s disease: a protein considered to be a key to potential future therapies.
The leucine-rich repeat kinase 2 (LRRK2) protein will be the focus of an experiment conducted on the Space Station. It is hoped that the microgravity conditions aboard the Space Station will allow growth of larger, more regular LRRK2 protein crystals, which would help scientists solve the protein’s structure — providing valuable information for the design of optimized therapies to fight Parkinson’s disease (PD).
The experiment is the result of a partnership between the Michael J. Fox Foundation for Parkinson’s Research and the Center for the Advancement of Science in Space (CASIS).
“We’re thrilled that PD research has been selected to travel to the International Space Station and honored to partner with CASIS on behalf of the PD community here on Earth,” said Michael J. Fox, the actor who started the foundation after he was diagnosed with Parkinson’s, in a video message played at the International Space Station Research and Development Conference held in Washington, DC, July 17 – 20.
The SpaceX CRS-12 cargo resupply mission scheduled for liftoff in August will carry LRRK2 protein to the Space Station to be used in the Crystallization of LRRK2 Under Microgravity Conditions (CASIS PCG 7) experiment.
In its role as manager of the Space Station’s U.S. National Laboratory, CASIS is responsible for coordinating transfer of scientific materials to and from the Space Station and oversight of work conducted in the laboratory. The Michael J. Fox Foundation, which initiated this project, has supported earthside preparation of the protein for growth in space.
Advancing Understanding of LRRK2 as a Key Parkinson’s Drug Target
LRRK2 is considered to be the greatest known genetic contributor to Parkinson’s disease, according to the Michael J. Fox Foundation. Most Parkinson’s cases are categorized as “idiopathic” — of unknown cause — with only about 10 percent of cases having been linked to a genetic cause. LRRK2 gene mutations are the most common cause of Parkinson’s in that minority, which represents only 1 to 2 percent of total Parkinson’s cases.
However, LRRK2 mutations account for a much higher proportion of Parkinson’s cases among people of certain ethnic groups, notably Ashkenazi Jews, North African Arab Berbers, and Basques, than they do in the general population.
The foundation notes that while estimates vary, it is believed that mutated LRRK2 (predominantly the mutation scientists refer to as G2019S) account for some 15 to 20 percent of Parkinson’s cases among Ashkenazi Jews, and about 40 percent of cases in North African Arab Berbers. Also, other genetic changes in LRRK2 have been found to increase risk of developing Parkinson’s among people of other ethnic backgrounds, such as in Asians of Chinese descent.
Because LRRK2 protein function is heightened in people with Parkinson’s disease, and is associated with a mutation in the LRRK2 gene, the foundation believes therapies targeting this gene could also accelerate development of treatments that can benefit a broader Parkinson’s population.
However, one obstacle holding back this line of drug development is the limited understanding of LRRK2’s exact structure. The foundation notes that greater understanding of a protein’s shape and structure can help developers design therapies more likely to engage a particular protein in treatment of disease.
Overcoming Gravitational Limitations
Earth’s gravitational field allows only low resolution versions of LRRK2 protein to be grown. However, the Crystallization of LRRK2 Under Microgravity Conditions (CASIS PCG 7) experiment will use automated biotechnology devices operating in the microgravity environment to grow larger, better-formed protein crystals with fewer defects that may yield higher resolution views of LRRK2. These will then be returned to Earth for postflight analysis.
Having a better detailed view of the precise shape and morphology of LRRK2’s crystalline structure would help scientists better understand Parkinson’s pathology, and accelerate development of LRRK2 inhibitor therapies designed to prevent, slow, or stop Parkinson’s disease progression.
“The unique environment of the International Space Station untethers research from restrictions imposed by gravity,” CASIS president and executive director, Gregory H. Johnson, said in a press release. “CASIS is glad to partner with The Michael J. Fox Foundation to explore the structure of this important piece of the Parkinson’s puzzle.”
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