On March 4, 2012 Debbie Gregoire (mother to Chloe, Ring14) spoke with Anne Cherry regarding her upcoming IPS research on Chromosome Ring14. Anne is a graduate student at Harvard University, working on her Ph.D. in Biological Chemistry and Molecular Pharmacology. She studies stem cell research.
Stefania Azzali initiated a conversation with the head of Anne‘s department at Harvard regarding IPS and Ring14, and invited Anne to speak at the October, 2011 Workshop on Ring14 Syndrome. At that time, Anne presented to physicians, scientists, Ring14 family members, and others her proposed research on Ring14 and IPS cells, Induced Pluripotent Stem cells. Anne works in the Hematology Lab at Harvard and her work is primarily focused on a condition called Fanconi Anemia, which is a condition that involves the blood system. Her primary work is in determining why Fanconi Anemia cells cannot be reprogrammed into IPS cells.
Induced Pluripotent Stem (IPS) cells are cells that have been genetically reprogrammed to an embryonic or pre-embryonic stem cell state. Essentially, they are fully formed cells that are manipulated such that they can be taken back to the beginning state of cell production, before individual cells form their tissue function (e.g. finger, liver, eye, heart, etc.). Pluripotent means “many powerful. “ Once in this IPS state, study can begin of a particular disease, in this case Ring14.
As a result of her knowledge of IPS cells and her interest in Ring Chromosomes (which are considered a rarity), Anne is undertaking this Ring14 study. Anne will predominately be working alone on this project. Through the Ring14 BioBank in Italy, Anne is obtaining cells of two (2) Ring14 patients and one (1) parent each, for a total of four (4) cells. She will begin this study with skin cells. Anne has already received the skin cells of one Ring14 patient and their parent, and the second Ring14 patient and parent’s cells are soon to be received. The Ring14 parents involved in this study have been informed and have provided written consent. As soon as Anne receives this written consent, she will begin her study. Anne will be utilizing the laboratory at The Children’s Hospital of Boston for this work.
Skin cells are obtained by doing a “Punch Biopsy,” which uses an instrument called a punch to remove tissue. These skin cells are called “Fibroblasts” and are a part of the hypodermis layer of skin. The hypodermis is the third layer of skin, below the epidermis and dermis. Once obtained, the cells can be kept in a frozen state at -100 degrees Fahrenheit indefinitely.
The initial goal of the study is to get these skin cells turned into IPS cells. Fairly recent history shows that depending upon the disease some cells have effectively been turned into IPS cells in a matter of only a few weeks, while other condition’s cells, no matter how much time allowed, have been unsuccessful in turning into IPS cells. At this point, it is unknown if the Ring14 cells will effectively turn into IPS cells.
Should the study work, the benefits have the potentiality of being great. The biggest benefit is that IPS cells can grow and reproduce forever, providing literally thousands of Ring14 cells for future and further study by Neuroscientists, scientists who study the brain and neurons. Studies can then be undertaken to determine how the Ring affects the cells of an effected Ring14 patient.
Anne explained that typically Ring14 patients fall into one of two categories: some patients have completely intact 14th chromosomes, with no missing or added genetic material, but for some reason the chromosome turned into a ring. The second type of Ring14 patients may be more complicated with either missing 14th chromosome DNA, added DNA to the 14th chromosome, or a combination of both while simultaneously forming a ring. There is a third Chromosome 14 anomaly subset, which is a patient that does not have a ring but has added DNA, deleted DNA or a combination of these two factors on the 14th chromosome. By making the IPS cells, the researchers can compare complete rings with added/deleted or combination rings to learn more about the Ring14 condition.
Anne will first be studying the complete ring as she feels it has the best chance of turning into IPS cells successfully. In the two family samples that Anne is working with, one patient has a complete ring and the second patient has a more complicated ring with either a deletion or an addition. As I said, Anne will first work with the complete ring, anticipating more initial success with this less complicated ring. If Anne is successful at turning the complete ring into IPS cells, and if the Ring14 community is fortunate enough to get a Neuroscientist involved in continued research, Anne is agreeable to trying to turn the more complicated Ring14 cells into IPS for neuroscientific study. Having these IPS cells available, Neuroscientists will then be able study how the Ring14 chromosome behaves in different cell types.
In doing the IPS study, Anne will have a “control” sample (the parent’s cells) to develop baseline data, and an experimental sample (the Ring14 patient’s cells). Comparisons can then be made between the healthy cells and the afflicted cells. With these IPS cells, researchers can learn more about the Ring14 disease.
The biggest potential benefit of successful IPS reprogramming and study by the neuroscientific community is the potentiality of targeted medications to treat symptoms of Ring14 (e.g., seizures, motor skills, development delay, etc.). By studying the DNA, medications could be produced or made available to lessen Ring14 characteristics. In deriving an effective drug therapy, neuroscientists can target specific drugs directly to the IPS/neuronal cells.
Anne explained that often a first pass at IPS cell reprogramming doesn’t work, but she is utilizing a new approach which she feels offers promise for Ring14 cells. She anticipates that it will take a couple of months to get the first sample reprogrammed. Having the first set of samples on-hand, Anne is just waiting for the family’s sign-off, and she will immediately begin the study. The study should likely last only a few months, at which time, if successful, Anne will have compiled thousands of Ring14 IPS cells, kept in a frozen state, available for future research. The beauty of this is that there should be an abundance of cells that are available for current and future research.
In order to move forward, anticipating a successful IPS reprogramming, it is critical that the Ring14 community receive collaboration from a Neuroscientist who can take these collected IPS cells and further study them. Anne’s background in this type of project is solely in turning skin cells into IPS cells. Future study of these cells must be conducted by a Neuroscientist who can turn the IPS cells into neurons for research which will potentially lead to drug therapies.
Anne’s main contact point in the Ring14 community is Stefania Azzali. Results of her findings will be reported directly to Stefania.
The Ring14 community is most thankful the Anne for her research efforts.