Partner Therapeutics Announces Publication of Results from Pre-Clinical Study Evaluating Recombinant Murine GM-CSF in Mouse Models of Down Syndrome and Normal Aging

Pre-clinical study with recombinant murine GM-CSF reversed cognitive impairment in Dp16 model of Down syndrome and improved cognitive function in aged normal mice

The CU Anschutz Medical Campus team recently awarded a grant from the National Institutes of Health/National Institute on Aging to study Leukine® treatment in young adults with Down syndrome

Lexington, MA – March 29, 2022 — Partner Therapeutics, Inc. (PTx), a commercial biotech company, announces publication of results from investigator-sponsored pre-clinical research evaluating use of recombinant murine GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) to improve cognitive ability and brain pathology in an aged mouse model of Down syndrome and in aged normal mice.  “The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 down syndrome mice and improves learning/memory in wild-type mice” (Ahmed et al.) was published online on March 18, 2022 by Neurobiology of Disease, an Elsevier journal.

This research was conducted at the University of Colorado Anschutz Medical Campus by a multidisciplinary team led by Md. Mahiuddin Ahmed, PhD, with co-senior authors Huntington Potter, PhD. and Tim Boyd, PhD.  People with Down syndrome are at higher risk for Alzheimer’s, and previous work showed that GM-CSF improves cognition and brain pathology in AD mice and that Leukine® (sargramostim, glycosylated, yeast-derived rhuGM-CSF) improved cognition and reduced blood biomarkers of neuronal damage in human AD patients. The new study shows that GM-CSF also, unexpectedly, improves cognition in mice that do not have Alzheimer’s disease pathology. “Discovering a treatment that may help children and young adults with Down syndrome to develop their physical and mental capabilities is critical to improving their health and activities of daily living,” said senior author Huntington Potter, PhD, professor of neurology at the University of Colorado School of Medicine, director of the University of Colorado Alzheimer’s and Cognition Center and director of Alzheimer’s disease research at the Linda Crnic Institute for Down Syndrome.

While these results showed that GM-CSF improved memory in Down syndrome mice, as well as in mice undergoing the typical aging, the potential effects in people with Down syndrome are yet unknown. Correspondingly, the CU Anschutz Medical Campus team was recently awarded a grant from the National Institutes of Health/National Institute on Aging to study Leukine treatment in young adults with Down syndrome. CU investigators will study its safety, potential effects on cognitive function, quality of life measures and biomarkers associated with neuronal damage.

The new NIH-funded project, co-directed by Potter and Peter Pressman, MD, from the CU department of neurology, will leverage collaborations between research teams on the CU Anschutz Medical Campus and at Colorado State University. They will work closely with the Linda Crnic Institute for Down Syndrome, which is an affiliate of the Global Down Syndrome Foundation (GLOBAL). GLOBAL is the leading Down syndrome organization successfully advocating for Down syndrome research funding at the NIH.

In the current pre-clinical study, Dr. Ahmed studied GM-CSF safety, tolerability and effects on behavior and brain pathology in the Dp16 (Dp[16]1Yey) mouse model of Down syndrome and in aging normal mice. Results showed that about one month of daily GM-CSF treatment reversed learning and memory deficits, reversed the loss of certain nerve cells, and markedly reduced the abnormal activation of the nerve-supporting astrocyte cells in the brains of the Dp16 mice.  About one month of daily GM-CSF also improved cognitive function in normal aging mice.

Dr. Potter also recently published encouraging preliminary clinical results of a randomized, double-blind, placebo-controlled Phase II trial that tested the safety and efficacy of Leukine treatment in participants with mild-to-moderate Alzheimer’s disease (NCT01409915). Top-line results of that trial are found in this article: DOI: 10.1002/trc2.12158

“We are breaking new ground in studying sargramostim for multiple, different disorders – Down syndrome and Alzheimer’s disease,” Potter said. “We hope that this therapy, already proven to be safe for other diseases, has the potential to improve cognitive function in people with Down syndrome.”  Further research will be undertaken to determine whether Leukine is safe, tolerable and efficacious in people with Down syndrome. 



PTx, an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit

Important Safety Information for Leukine (sargramostim)


  • LEUKINE is contraindicated in patients with known hypersensitivity to human granulocyte-macrophage colony stimulating factor such as sargramostim (GM-CSF), yeast-derived products, or any component of LEUKINE.

Warnings and Precautions

  • Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If any serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy and institute medical management. Permanently discontinue LEUKINE in patients with serious allergic reactions.
  • LEUKINE can cause infusion-related reactions, including respiratory distress, hypoxia, flushing, hypotension, syncope and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease, as dose adjustment or discontinuation may be required.
  • Do not administer LEUKINE simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
  • Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported in patients after LEUKINE administration. LEUKINE should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
  • Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
  • If ANC > 20,000 cells/mm3 or if WBC counts > 50,000/mm3, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
  • LEUKINE therapy should be discontinued if disease progression is detected during treatment.
  • Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration required.
  • Liquid solutions containing benzyl alcohol (including LEUKINE Injection) or LEUKINE for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates and low birth weight infants.
  • Concomitant use of drugs that can potentiate the myeloproliferative effects of LEUKINE should be avoided.

Adverse Reactions

Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported in a higher frequency than placebo are:

  • In Autologous bone marrow transplantation (BMT) patients–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
  • In Allogeneic BMT patients–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
  • In AML patients–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema


Bill McClements

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