Dan (San Jose, CA) is a supporter of NeoLymeMed Team. When he heard about GoFundMe campaign on Lyme disease and Post Treatment Lyme disease syndrome (PTLDS), he shared his experience to our NeoLymeMed Team and the supporters of this drive.
Here is Dan’s Story:
While hiking in San Mateo, CA in 2006 I noted a tick on my arm. I flicked it off. When I got home to San Jose I noted a red circle on my calf. Each day the red circle got larger and was white in the center. My second-grade daughter told me she had just studied that day about something called “Lyme’s disease.” I had never heard of it. She recognized the tell-tale “bulls’ eye” on my leg. The next day I was sitting at my desk in my office when I felt a spike-like jab in my big toe. This too I learned, was a symptom of Lyme’s. I went to see my doctor at Kaiser (St. Teresa). I was adamantly told that there was no Lyme’s disease in our area. I asked what had caused the bull’s eye on my leg; they didn’t know. They offered no treatment. After reading about the disease on the internet, I decided to take matters into my own hands. I have many medications in my drawer, from a lifetime of illnesses. I took 10 days of Doxycycline bid. The pain never recurred; the spot cleared up, and I feel that Providence intervened, and I dodged a bullet. I have a dear friend whose life has been turned upside down from Lyme’s disease.
I wholeheartedly support efforts to treat this disease and give a normal life back to those who suffer from Lyme’s destruction.
The quest for the solution by our Team:
Developing new therapy for acute and post-treatment Lyme disease syndrome with one drug for both anti-inflammatory and anti-persister
In a Nut Shell:
Lyme disease is caused by a bacteria called Borrelia burgdorferi that is spread by the Ixodes scapularis ticks. About 10-20% of Lyme patients treated with prescribed antibiotic therapy reports the recrudescence of symptoms, such as muscle and joint pain, psycho-social and cognitive difficulties, and generalized fatigue. This condition is referred to as Post-treatment Lyme Disease Syndrome (PTLDS). One of us has recently discovered that one of the FDA approved drug, which has an anti-persister effect on doxycycline-surviving B. burgdorferi. We also found that drug cleared B. burgdorferi infection and reduced the inflammation in C3H/HeN mouse. With an aim to take our drug to Lyme disease affected patients, we are developing a novel oral formulation of the drug and will study pharmacokinetic/pharmacodynamics (PK/PD) in rats. Our discovery has promising potential to develop a novel treatment for both acute Lyme disease and post-treatment Lyme disease syndrome.
I will contribute this money to PTLDS research to achieve the following research aims. I am pretty sure that even this little money will make some impact on PTLDS therapeutics.
In this project, we will develop a clearer understanding of the mechanisms by which antibiotic kills B. burgdorferi in both in vitro and in an in vivo mice model. In addition to it, we will test our novel oral formulation in Sprague Dawley rats. We have listed our millstones in detail below.
1) Studying antibiotic role in T cells response and macrophage polarization in C3H mice. Immunophenotyping of T cells and macrophages $28,800
2) Measurement of inflammatory mediators in serum and cell-free supernatants of BMDM cultures $10,900
3) Quantitative real-time PCR $3,200
1) Synthesizing biotinylated-derivative of the antibiotic and fluorescent labeled antibiotic $3,300
2) Isolating binding partner(s) of antibiotic via pull-down assays with streptavidin beads $4,500
3) Identification of binding partner(s) using LC-MS/MS $7,400
1) Preparation of oral formulation of antibiotic $19,200
2) Studying pharmacokinetics (PK) and pharmacodynamics (PD) for novel formulations of antibiotic in Sprague Dawley rats $19,800
3) Evaluation of samples by mass spectrometry $2,900
Though the exact reason for the cause of PTLDS is not known but there is an unmet need for developing therapeutic agents. We have identified an antibiotic that kills both stationary phase and drug-tolerant B. burgdorferi at 20 μg/ml. When tested in in-vivo, antibiotic has shown good efficacy against B. burgdorferi infection in C3H/HeN mice model. Furthermore, that antibiotic reduced macrophage infiltration to spleen after 7 days of B. burgdorferi infection and decreases induction of M1 macrophages (NOS2+) with IFN-G+ response, which helps for Lyme disease progression. In addition to it, the antibiotic also reduced proinflammatory mediators responsible for Lyme disease propagation. With a goal to treat Lyme affected patients with the antibiotic, we have developed an oral formulation by encapsulating the antibiotic in alginate beads using ionotropic-external gelation technique and then enteric coated with eudragit S100. Our novel formulation has the ability to protect the antibiotic from acidic pH of stomach and releases drug only in intestine (at basic pH). Based on our preliminary data, we propose we will study how the immune system responds during infection and treatment with different drugs that are currently used for treating Lyme disease and also comparing with our lead molecule which has the ability to kill persisters. We will also test our novel oral formulation in rats and study pharmacokinetics (PK) and pharmacodynamics (PD).
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DonationsSee top donations
- Nagaraju Anugula
- Ravi Pamnani
- Uday Kumar
Organizer and beneficiary
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