\ ALS Research \ Current Status On Thrombopoietin
Susan Graham Walker
The ALS Association is actively investigating thrombopoietin (rhTPO) and its potential benefit for people with ALS. In aggressively collecting
information over the past several weeks, ALSA’s president, research
director and vice president, patient services have initiated multiple
discussions with several ALS science and clinical experts, representatives from the FDA, Genentech - the company that apparently holds the available rhTPO - and George Schwartz, MD, the physician who reported the ALS one-patient case study using rhTPO. We recognize the time-sensitive nature of the rhTPO issue.
How is ALSA helping?
We are actively urging more review and discussions about the study of rhTPO for ALS while we continue to gather more information about rhTPO, about Dr. Schwartz’s patient experience and about the scientific rationale for testing rhTPO in ALS. Additionally, we remain in frequent communication with all involved parties including the drug companies as we look into what next steps are necessary. ALSA staff is pursuing all avenues related to rhTPO on behalf of people with ALS while maintaining the highest scientific standards and concern for patient well-being.
A summary of the information we have gathered to date is included here in the format of frequently asked questions (FAQs).
What clinical trials have been conducted with rhTPO?
There have been a number of clinical studies evaluating the potential
benefit of rhTPO for use in cancer - related to possible treatment for the platelet reduction that can come with some chemotherapy. Other conditions for which rhTPO has been studied are those that cause thrombocytopenia.
Thrombocytopenia is a medical term for a reduction of blood platelets.
These clinical trials have not led to FDA approval for any indication, and rhTPO remains an experimental compound.
What is the scientific rationale for how rhTPO might provide a benefit for people with ALS?
RhTPO is known to be a growth factor that stimulates the production of platelets and other primitive blood cells. It is theorized that platelet
growth factors might have a neuroprotective effect on the motor nerves.
This has not been proven yet in an ALS animal model or in humans.
The rationale for testing rhTPO in a clinical study of ALS is that
elevation of the platelet counts may result in a release from platelets of several different growth factors with possible subsequent diffusion into the central nervous system. A working hypothesis of this study is that these platelet growth factors might exhibit trophic and protective
features for motor neurons.
What studies have been done with rhTPO in ALS and what is planned?
· Through our extensive Internet research, we have found citations for a few scientific studies that may tangentially support the rationale for
testing rhTPO in ALS. We have forwarded these citations to ALS experts and are in the process of obtaining copies of these articles and reviewing them as possible supportive literature for defining the science basis for
rhTPO in ALS.
· An ALS one-patient case study from Dr. Schwartz using rhTPO has been reported at a recent scientific meeting. ALSA is obtaining the abstract and any publications related to this case study report, and has requested additional information and literature from Dr. Schwartz.
· Mouse TPO is now being tested in an ALS mouse model at the Massachusetts General Hospital (MGH). This study is in its early stages of investigation and ALSA maintains close communication with the investigators.
· These same ALS investigators at MGH have a protocol prepared for a 10-patient, safety study of rhTPO. Moving forward with this human trial is dependent on obtaining rhTPO, which is not currently available to the investigators. ALSA is aggressively working to make the existing supply of rhTPO available for this human trial.
Why is rhTPO not available for the small human ALS study?
Although a small amount of rhTPO exists, the company Pharmacia holds the rights for further development and production of rhTPO. ALSA is in contact with both Genentech and Pharmacia concerning rhTPO and how to find a way to make the existing supply available for a clinical trial.
What is thrombopoietin?
TPO is a hormonal substance, made largely in the liver and bone marrow of
humans and other mammals, and is found in the body’s plasma. Identified in the 1950s, TPO was recognized as acting to increase the number of platelets in the blood in situations in which the body’s level of circulating platelets drops below a key level.
Recombinant human thrombopoietin (rhTPO) is an investigational agent (meaning that it is not FDA approved). It stimulates megakaryocyte
production and raises the circulating platelet count. Megakaryocytes are large cells in the bone marrow that release mature platelets. Platelets contain several different growth factors that have demonstrated in vitro and in vivo to have trophic actions for motor neurons. In vitro means in a laboratory environment such as a test tube or dish, and in vivo means in a living body – animal or human.
What is recombinant?
This is the technology of making combinations of materials using human DNA sequences. This technology process is used to make novel products or compounds or to develop a commercial product of a naturally occurring human biologic or chemical substance. The “r” indicates it is made by recombinant technology and the “h” refers to human.
When is rhTPO not recommended or not suitable and what are known side effects?
Cautions for the potential use of rhTPO in humans include those people with known prior hypersensitivity to recombinant forms of thrombopoietin, and active thromboembolic disorder. Care should be taken with people who have blood clotting disorders, prior blood clots, cardiovascular disease, kidney or liver insufficiency, and prior pelvic radiation.
The risks of blood clots and thromboembolism (clots traveling to the legs, lungs, brain, heart or other body areas) are not known and are underinvestigation. Previous trials with rhTPO for cancer patients may not provide the same side effect information as a trial in ALS would provide with rhTPO, due to potential differences in dosage and/or length of treatment.
ALSA will continue to keep the ALS community informed of new information regarding rhTPO.
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Current Status On Thrombopoietin
With permission of the ALS Association we are 'reprint' the following statement on this area of investigation.Susan Graham Walker
The ALS Association is actively investigating thrombopoietin (rhTPO) and its potential benefit for people with ALS. In aggressively collecting
information over the past several weeks, ALSA’s president, research
director and vice president, patient services have initiated multiple
discussions with several ALS science and clinical experts, representatives from the FDA, Genentech - the company that apparently holds the available rhTPO - and George Schwartz, MD, the physician who reported the ALS one-patient case study using rhTPO. We recognize the time-sensitive nature of the rhTPO issue.
How is ALSA helping?
We are actively urging more review and discussions about the study of rhTPO for ALS while we continue to gather more information about rhTPO, about Dr. Schwartz’s patient experience and about the scientific rationale for testing rhTPO in ALS. Additionally, we remain in frequent communication with all involved parties including the drug companies as we look into what next steps are necessary. ALSA staff is pursuing all avenues related to rhTPO on behalf of people with ALS while maintaining the highest scientific standards and concern for patient well-being.
A summary of the information we have gathered to date is included here in the format of frequently asked questions (FAQs).
What clinical trials have been conducted with rhTPO?
There have been a number of clinical studies evaluating the potential
benefit of rhTPO for use in cancer - related to possible treatment for the platelet reduction that can come with some chemotherapy. Other conditions for which rhTPO has been studied are those that cause thrombocytopenia.
Thrombocytopenia is a medical term for a reduction of blood platelets.
These clinical trials have not led to FDA approval for any indication, and rhTPO remains an experimental compound.
What is the scientific rationale for how rhTPO might provide a benefit for people with ALS?
RhTPO is known to be a growth factor that stimulates the production of platelets and other primitive blood cells. It is theorized that platelet
growth factors might have a neuroprotective effect on the motor nerves.
This has not been proven yet in an ALS animal model or in humans.
The rationale for testing rhTPO in a clinical study of ALS is that
elevation of the platelet counts may result in a release from platelets of several different growth factors with possible subsequent diffusion into the central nervous system. A working hypothesis of this study is that these platelet growth factors might exhibit trophic and protective
features for motor neurons.
What studies have been done with rhTPO in ALS and what is planned?
· Through our extensive Internet research, we have found citations for a few scientific studies that may tangentially support the rationale for
testing rhTPO in ALS. We have forwarded these citations to ALS experts and are in the process of obtaining copies of these articles and reviewing them as possible supportive literature for defining the science basis for
rhTPO in ALS.
· An ALS one-patient case study from Dr. Schwartz using rhTPO has been reported at a recent scientific meeting. ALSA is obtaining the abstract and any publications related to this case study report, and has requested additional information and literature from Dr. Schwartz.
· Mouse TPO is now being tested in an ALS mouse model at the Massachusetts General Hospital (MGH). This study is in its early stages of investigation and ALSA maintains close communication with the investigators.
· These same ALS investigators at MGH have a protocol prepared for a 10-patient, safety study of rhTPO. Moving forward with this human trial is dependent on obtaining rhTPO, which is not currently available to the investigators. ALSA is aggressively working to make the existing supply of rhTPO available for this human trial.
Why is rhTPO not available for the small human ALS study?
Although a small amount of rhTPO exists, the company Pharmacia holds the rights for further development and production of rhTPO. ALSA is in contact with both Genentech and Pharmacia concerning rhTPO and how to find a way to make the existing supply available for a clinical trial.
What is thrombopoietin?
TPO is a hormonal substance, made largely in the liver and bone marrow of
humans and other mammals, and is found in the body’s plasma. Identified in the 1950s, TPO was recognized as acting to increase the number of platelets in the blood in situations in which the body’s level of circulating platelets drops below a key level.
Recombinant human thrombopoietin (rhTPO) is an investigational agent (meaning that it is not FDA approved). It stimulates megakaryocyte
production and raises the circulating platelet count. Megakaryocytes are large cells in the bone marrow that release mature platelets. Platelets contain several different growth factors that have demonstrated in vitro and in vivo to have trophic actions for motor neurons. In vitro means in a laboratory environment such as a test tube or dish, and in vivo means in a living body – animal or human.
What is recombinant?
This is the technology of making combinations of materials using human DNA sequences. This technology process is used to make novel products or compounds or to develop a commercial product of a naturally occurring human biologic or chemical substance. The “r” indicates it is made by recombinant technology and the “h” refers to human.
When is rhTPO not recommended or not suitable and what are known side effects?
Cautions for the potential use of rhTPO in humans include those people with known prior hypersensitivity to recombinant forms of thrombopoietin, and active thromboembolic disorder. Care should be taken with people who have blood clotting disorders, prior blood clots, cardiovascular disease, kidney or liver insufficiency, and prior pelvic radiation.
The risks of blood clots and thromboembolism (clots traveling to the legs, lungs, brain, heart or other body areas) are not known and are underinvestigation. Previous trials with rhTPO for cancer patients may not provide the same side effect information as a trial in ALS would provide with rhTPO, due to potential differences in dosage and/or length of treatment.
ALSA will continue to keep the ALS community informed of new information regarding rhTPO.
| Posted On: Friday, April 11, 2003 Modified: Friday, April 11, 2003 Category: ALS Research Posted By: |